Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-α]pyrrolo[2,3-e]-pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof
The present disclosure relates to processes for preparing (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide, solid state forms thereof, and corresponding pharmaceutical compositions, methods of treatment (including treatment of rheumatoid arthritis), kits, methods of synthesis, and products-by-process.
1. A crystalline anhydrate of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.
2. The crystalline anhydrate of claim 1 , having an X-ray powder diffraction pattern characterized by peaks at 4.0±0.2, 14.5±0.2, and 19.0±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
3. The crystalline anhydrate of claim 2 , having an X-ray powder diffraction pattern characterized by an additional peak at 14.2±0.2.
4. The crystalline anhydrate of claim 3 , having an X-ray powder diffraction pattern characterized by an additional peak at 9.7±0.2.
5. The crystalline anhydrate of claim 4 , having an X-ray powder diffraction pattern characterized by an additional peak at 20.3±0.2.
6. The crystalline anhydrate of claim 1 , wherein the crystalline anhydrate is Freebase Anhydrate Form D of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.
7. The crystalline anhydrate of claim 1 , having an X-ray powder diffraction pattern substantially as shown in FIG. 3J .
8. The crystalline anhydrate of claim 1 , having a thermogravimetric analysis profile substantially as shown in FIG. 4I .
9. The crystalline anhydrate of claim 1 , having a differential scanning calorimetry profile substantially as shown in FIG. 5E .
10. The crystalline anhydrate of claim 1 , having a differential scanning calorimetry profile comprising an endotherm between about 180° C. and about 220° C. when heated at a rate of 10° C./minute.
11. The crystalline anhydrate of claim 1 , having a moisture sorption isotherm profile substantially as shown in FIG. 6D .
12. The crystalline anhydrate of claim 1 , having an orthorhombic lattice type that has a P2 1 2 1 2 space group, a unit cell a value of about 43.8 Å, a unit cell b value of about 8.6 Å, and a unit cell c value of about 9.2 Å.
13. A composition comprising a solid state form, wherein the solid state form is Freebase Anhydrate Form D of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.
14. The composition of claim 13 , comprising at least about 75% by weight of the Freebase Anhydrate Form D of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.
15. The composition of claim 13 , comprising at least about 95% by weight of the Freebase Anhydrate Form D of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.
16. A pharmaceutical composition comprising Freebase Anhydrate Form D of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and a pharmaceutically acceptable carrier.
17. The pharmaceutical composition of claim 16 , wherein the pharmaceutical composition comprises the Freebase Anhydrate Form D in an amount sufficient to deliver about 7.5 mg of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.
18. The pharmaceutical composition of claim 16 , wherein the pharmaceutical composition comprises the Freebase Anhydrate Form D in an amount sufficient to deliver about 15 mg of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.
19. The pharmaceutical composition of claim 16 , wherein the pharmaceutical composition comprises the Freebase Anhydrate Form D in an amount sufficient to deliver about 30 mg of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.
20. The pharmaceutical composition of claim 16 , wherein the pharmaceutical composition comprises the Freebase Anhydrate Form D in an amount sufficient to deliver about 45 mg of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.
21. A composition comprising a solid state form, wherein the solid state form is the crystalline anhydrate of claim 2 .
22. The composition of claim 21 , comprising at least about 75% by weight of the crystalline anhydrate.
23. The composition of claim 21 , comprising at least about 95% by weight of the crystalline anhydrate.
24. A pharmaceutical composition comprising the crystalline anhydrate of claim 2 and a pharmaceutically acceptable carrier.
25. The pharmaceutical composition of claim 24 , wherein the pharmaceutical composition comprises the crystalline anhydrate in an amount sufficient to deliver about 7.5 mg of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.
26. The pharmaceutical composition of claim 24 , wherein the pharmaceutical composition comprises the crystalline anhydrate in an amount sufficient to deliver about 15 mg of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.
27. The pharmaceutical composition of claim 24 , wherein the pharmaceutical composition comprises the crystalline anhydrate in an amount sufficient to deliver about 30 mg of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.
28. The pharmaceutical composition of claim 24 , wherein the pharmaceutical composition comprises the crystalline anhydrate in an amount sufficient to deliver about 45 mg of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.
29. A process for preparing the pharmaceutical composition of claim 16 , the process comprising combining the Freebase Anhydrate Form D of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and the pharmaceutically acceptable carrier.
30. A process for preparing the pharmaceutical composition of claim 24 , comprising combining the crystalline anhydrate and the pharmaceutically acceptable carrier.